We plan to enable advanced biological research in the RCE; testing, selection and improvement of our biodetection systems; and eventually transfer of the systems as reliable and effective tools for emergency response to a bioterrorist event or infectious disease. Specific Aims that we plan to support immediately include: Specific Aim 1. Micro/nanofluidics-mass spectrometry biosensors. Immunology, mass spectrometry (MS) and micro/nanofluidics techniques will be integrated to facilitate both the discovery of pathogen protein antigens and the assay for their presence in biological fluids. Specific Aim 2. Nanoelectromechanical biosensors. Label-free microfluidics-embedded nanoelectromechanical biosensing devices can detect individual pathogens, and will be refined to achieve single-molecule sensitivity for genomic and proteomic array profiling of pathogens. Specific Aim 3. Ultrasensitive optical biosensors. A set of advanced optical sensing technologies based on PCS and FRET will be developed for capable of detection bio markers at single molecule and SNP level, it can rapidly and specifically detect biomarkers, RNA/DNA and proteins. Specific Aim 4. Nanoelectrochemical biosensors. Using the electrochemical enzyme-multiplied immunoassay technique (ElectroEMIT), we can detect biospecies with ultrahlgh sensitivity (parts per billion) and specificity. Specific Aim 5.[unreadable]Lab-on-a-chip sampling technique. Simple liquid manipulation techniques based on the ElectroWetting-On-Dielectric (EWOD) mechanism can realize complex sample preparation procedures on-chip in a way suitable for portable biodetection systems.